Atezolizumab + Stereotactic Radiation in Triple-negative Breast Cancer and Brain Metastasis

NCT03483012 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-519
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying the combination of a drug called atezolizumab and a radiation procedure called stereotactic radiosurgery (SRS) as a possible treatment for triple-negative breast cancer that has spread to the brain. The interventions involved in this study are:

• Atezolizumab
• Stereotactic radiosurgery (SRS)

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  Defined as time from first dose of atezolizumab (day 1 cycle 1) to progression or death due to any cause. Progression is defined according to the bi-compartmental model proposed in the RANO-BM publication, and is defined as the first detection of radiologic progression of intracranial (per RANO-BM criteria), extracranial (per RECIST 1.1 criteria), or both or unequivocal progression of non-measurable disease in the opinion of the treating physician; with each compartment (CNS and non-CNS) assessed separately

  Assessed from the first dose of atezolizumab until the date of first documented progression according to RANO-BM or date of death from any cause, whichever came first, for a maximum of 1.5 years

Secondary Outcomes (2)

• Extracranial Objective Response Rate

  Assessed from the first dose of atezolizumab until disease progression, intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, for a maximum of 1.5 years

• Overall Survival

  Assessed from the first dose of atezolizumab to the date of death from any cause or date last known alive, for a maximum of 3.8 years

Study Arms (1)

Atezolizumab + Stereotactic radiosurgery (SRS)

EXPERIMENTAL

* Atezolizumab administered intravenously once every 3 weeks * Stereotactic radiosurgery (SRS) begin within 14 days after brain MRI obtained

Drug: Atezolizumab; Procedure: Stereotactic radiosurgery (SRS)

Interventions

Atezolizumab DRUG

Atezolizumab is a protein that affects your immune system by blocking the PD-L1 pathway

Also known as: Tecentriq

Atezolizumab + Stereotactic radiosurgery (SRS)

Stereotactic radiosurgery (SRS) PROCEDURE

Stereotactic radiosurgery (SRS) is a standard procedure used to treat patients with cancer in the brain. SRS uses many precisely focused radiation beams to treat tumors

Atezolizumab + Stereotactic radiosurgery (SRS)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed Stage IV invasive breast cancer. Participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation.
• Either the primary tumor and/or metastatic tumor must be triple-negative as defined below:
• Hormone receptor status: the invasive tumor must be ER- and PR-negative, or staining present in \<1% by immunohistochemistry (IHC)
• HER2 status: the invasive tumor must be Human Epidermal Growth Factor Receptor 2 Negative (HER2-negative) by the ASCO CAP guidelines
• In cases where both primary tumor and metastatic sample(s) have been tested for ER, PR, and HER2, the triple-negative status of the most recent sample should be used.
• Participants must have a diagnosis of brain metastases for which SRS is indicated, as determined by a radiation oncologist.
• The contrast-enhancing intraparenchymal brain metastases(s) must be well circumscribed and must have a maximum diameter of ≤ 3.0 cm in any direction on the enhanced scan.
• Participants must not have more than 5 new or progressive lesions in the brain requiring SRS treatment (greater than 5 total brain lesions are allowed as long as no more than 5 lesions require SRS treatment).
• Participants must have measurable extracranial disease as defined by RECIST 1.1.
• Participants must be willing to undergo a research biopsy at baseline and at Cycle 2 Day 1 if extracranial metastases are safely accessible. Participants for whom biopsies cannot be safely performed must be willing to submit an archival primary and/or metastatic specimen. The biopsies may be waived with prior PI approval for the first 6 participants enrolled to the safety run in phase.
• Prior systemic therapy:
• Participants must have discontinued systemic therapy at least 14 days prior to initiating protocol therapy.
• There is no limit to the number of prior lines of systemic therapy. Participants who have not received any systemic therapy for metastatic disease are also eligible.
• Participants may initiate or continue bisphosphonate therapy on study.
• Prior local therapy:

You may not qualify if:

• CNS complications for whom urgent neurosurgical intervention is indicated (e.g., resection, shunt placement).
• Known leptomeningeal or brainstem metastases. The presence of leptomeningeal enhancement alone, without associated clinical manifestations and/or positive CSF cytology, will not be constituted as known leptomeningeal metastases.
• Treatment with high dose systemic corticosteroids defined as dexamethasone \>2mg/day or bioequivalent within 7 days of initiating therapy.
• Patients unable to undergo gadolinium contrast-enhanced MRI or receive IV contrast for any reason (e.g., due to pacemaker, ferromagnetic implants, claustrophobia, extreme obesity, hypersensitity).
• Participants who are receiving any other investigational agents.
• Previous treatment with any anti-PD-1, PD-L1, or PD-L2 agent.
• Subjects with a history of hypersensitivity to compounds of similar biologic composition to atezolizumab or any constituent of the product
• The participant has an uncontrolled intercurrent illness, including, but not limited to uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, congestive heart failure-New York Heart Association Class III or IV, active ischemic heart disease, myocardial infarction within the previous six months, uncontrolled diabetes mellitus, gastric or duodenal ulceration diagnosed within the previous 6 months, severe malnutrition or psychiatric illness/social situations that would limit compliance with study requirements.
• Participant has a medical condition that requires chronic systemic steroid therapy or on any other form of immunosuppressive medication. For example, patients with autoimmune disease that requires systemic steroids or immunosuppression agents should be excluded. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has evidence of active, noninfectious pneumonitis that requires treatment with steroids.
• Has a history of interstitial lung disease.
• The participant is known to be positive for the human immunodeficiency virus (HIV), HepBsAg, or HCV RNA. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with atezolizumab.
• Individuals with a history of different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years or are deemed by the principal investigator to be at low risk for recurrence of that malignancy.
• Has received a live vaccine within 28 days of planned start of study therapy.
• The participant is pregnant or breast-feeding.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Giordano A, Graham N, Aizer AA, Tayob N, Pereslete AM, Schoenfeld JD, Leone JP, Davis R, Erick TK, Mayer EL, Winer EP, Krop I, Tolaney SM, Lin NU. A phase II study of atezolizumab in combination with stereotactic radiation for patients with triple-negative breast cancer and brain metastasis. Breast Cancer Res Treat. 2026 Mar 7;216(2):24. doi: 10.1007/s10549-026-07932-6.

  PMID: 41793510 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

atezolizumab; Radiosurgery

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Sara Tolaney, MD, MPH
• Organization: Dana-Farber Cancer Institute

Sara_Tolaney@dfci.harvard.edu

617-632-5743

Study Officials

• Nancy U Lin, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 28, 2018
• First Posted: March 29, 2018
• Study Start: May 1, 2018
• Primary Completion: November 21, 2019
• Study Completion: November 12, 2025
• Last Updated: April 21, 2026
• Results First Posted: December 22, 2023

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)